Generation of Aptamer-Molecularly Imprinted Polymer Hybrid Materials
Lead Research Organisation:
The Open University
Department Name: Life, Health & Chemical Sciences
Abstract
Molecular recognition (the ability to specifically recognise a chemical compound) is a highly important feature of analytical science. More often than not compound specific recognition comes from biological element such as enzymes, antibodies and DNA. Aptamers are short strands of DNA.
Whilst the properties in terms of recognition for biological molecules are excellent, the performance and environmental stability is low and this can compromise their uses. In particular degradation is a major problem.
To combat these derogatory issues a new generation of artifical recognition materials have been developed. At the forefront is a technology called Molecular Imprinting. This involves making a small binding pocket in a polymer which is chemically and shape specific for the target compound. These "smart plastics" offer the robustness and the ability to work in extreme environmental conditions but can lack the needed specificity/affinity.
This project aims to create a "best of both worlds" scenario. By slightly changing the chemical structure of the aptamer DNA we intend to use the aptamer as the recognition part of a molecularly imprinted polymer (MIP). This will be achieved by making the aptamer polymerisable so it can become part of the polymer structure, incorporating it into the polymer matrix via polymerisable groups on the DNA.
In this way we intend to preserve the high affinity and specificity of the aptamer whilst imparting the robustness and added shape specificity generated by the MIP. The presence of the polymer should protect the aptamer from environmental degradation and potentially widen the scope of use of aptamers for recognition.
Whilst the properties in terms of recognition for biological molecules are excellent, the performance and environmental stability is low and this can compromise their uses. In particular degradation is a major problem.
To combat these derogatory issues a new generation of artifical recognition materials have been developed. At the forefront is a technology called Molecular Imprinting. This involves making a small binding pocket in a polymer which is chemically and shape specific for the target compound. These "smart plastics" offer the robustness and the ability to work in extreme environmental conditions but can lack the needed specificity/affinity.
This project aims to create a "best of both worlds" scenario. By slightly changing the chemical structure of the aptamer DNA we intend to use the aptamer as the recognition part of a molecularly imprinted polymer (MIP). This will be achieved by making the aptamer polymerisable so it can become part of the polymer structure, incorporating it into the polymer matrix via polymerisable groups on the DNA.
In this way we intend to preserve the high affinity and specificity of the aptamer whilst imparting the robustness and added shape specificity generated by the MIP. The presence of the polymer should protect the aptamer from environmental degradation and potentially widen the scope of use of aptamers for recognition.
Planned Impact
Successful development of aptamer-MIP hybrid materials would pave the way for a new generation of molecularly imprinted polymers. By improving the recognition properties of this class of polymer it would pave the way for their use to become more mainstream, offering significant commercial gain.
The benefits to the aptamer community would be high as well. Currently uses of them are often limited by environmental considerations. Incorporation into a robust material whilst maintaining mode of action would be a benefit for several uses and this has clear commerical aspects.
The development of novel DNA chemistry, proposed in this paper opens up futher methods to interact DNA with other materials, especially materials considered to be "artificial". This marrying of biological and synthetic technology would be invaluable.
If successful this work will open up a new avenue of research, with will benefit the wide community and help position the PI as world leaders in novel recognition elements.
Additionally, any peer-reviewed publications arising from this grant will be registered on the Open University's open access institutional repository - Open Research Online (ORO) at http://oro.open.ac.uk. ORO is now one of the largest HEI repositories in the UK with over 850,000 visits from people in 170 countries since 2006. It enables access to research outputs via common search engines including Google, by using the OAI (Open Archives Initiative) Protocol for Metadata Harvesting.
The benefits to the aptamer community would be high as well. Currently uses of them are often limited by environmental considerations. Incorporation into a robust material whilst maintaining mode of action would be a benefit for several uses and this has clear commerical aspects.
The development of novel DNA chemistry, proposed in this paper opens up futher methods to interact DNA with other materials, especially materials considered to be "artificial". This marrying of biological and synthetic technology would be invaluable.
If successful this work will open up a new avenue of research, with will benefit the wide community and help position the PI as world leaders in novel recognition elements.
Additionally, any peer-reviewed publications arising from this grant will be registered on the Open University's open access institutional repository - Open Research Online (ORO) at http://oro.open.ac.uk. ORO is now one of the largest HEI repositories in the UK with over 850,000 visits from people in 170 countries since 2006. It enables access to research outputs via common search engines including Google, by using the OAI (Open Archives Initiative) Protocol for Metadata Harvesting.
People |
ORCID iD |
Nicholas Turner (Principal Investigator) |
Publications
Brahmbhatt H
(2016)
Improvement of DNA recognition through molecular imprinting: hybrid oligomer imprinted polymeric nanoparticles (oligoMIP NPs).
in Biomaterials science
Poma A
(2014)
Nucleoside-Tailored Molecularly Imprinted Polymeric Nanoparticles (MIP NPs)
in Macromolecules
Poma A
(2015)
Generation of novel hybrid aptamer-molecularly imprinted polymeric nanoparticles.
in Advanced materials (Deerfield Beach, Fla.)
Sullivan MV
(2021)
Hybrid Aptamer-Molecularly Imprinted Polymer (aptaMIP) Nanoparticles from Protein Recognition-A Trypsin Model.
in Macromolecular bioscience
Description | The proposal was to study a new type of molecularly imprinted polymer using an aptamer (single strand DNA chain) as a recognition element for small molecules. New polymeric materials were developed which allow for the incorporation of aptamers via the use of a polymerisable thymine base, into nanoparticles. Studies into suitable polymerisable bases were carried out. Nanoparticles were developed for: 1: Base recognition (A-T) DOI: 10.1021/ma501530c 2: DNA sequence recognition (12 base pair recognition using complimentary strands)10.1039/C5BM00341E 3: Small molecule recognition (cocaine) DOI: 10.1002/adma.201404235 |
Exploitation Route | The demonstration of this opens up a wide range of areas. A number of further studies into the particular chemistries exist including: * exploring different chemistries for DNA (aptamer) attachment to polymers to expand potential flexibility of this technique. * exploring the use of the MIP polymer scaffold as a protective device for aptamer technologies. * exploring the possibility of DNA sequence recognition (longer sequences, sequence mismatch) * incorporation of signal transduction onto nanoparticles. * further development of materials for bioactive compounds for both sensing and drug delivery. It is my intention to generate further applications to EPSRC within a collaborative network led by myself. 2017 : Further support for this work applied for to EPSRC. Project continuing via Santander fund targeting small proteins |
Sectors | Agriculture, Food and Drink,Chemicals,Environment,Pharmaceuticals and Medical Biotechnology |
Description | To early to tell though early discussions are occurring with an Aptamer research company. The results have been published and are currently being used for support for further funding. 2017 : NDA's signed. Aptamer group supported in kind for EPSRC bid follow up. 2018: Follow up grant submitted. awaiting result. Small travel grant was successful to allow for further experimentation, currently under study. 2019: Grant (EP/S003339/1) was submitted and successful. 2021: This has led to a full collaboration where details are explained in the follow-on grant submission. There is an exploration of improving the companies materials and development of new avenues of research. To Date we are looking at developing novel materials for detection of antibiotics and viral proteins, especially targeting COVID. while these materials are still in early stages the potential for robust detection methods offer significant potential impacts. This grant led to this point and i will update further on the next grant. |
First Year Of Impact | 2014 |
Sector | Agriculture, Food and Drink,Chemicals,Environment,Healthcare,Pharmaceuticals and Medical Biotechnology |
Impact Types | Economic |
Description | Exploration of Linking Chemistry in the Design of Aptamer-Molecularly Imprinted Polymer Hybrids (aptaMIPs) |
Amount | £294,568 (GBP) |
Funding ID | EP/S003339/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 07/2019 |
End | 07/2021 |
Description | Santander Resaerch Travel Award |
Amount | £4,800 (GBP) |
Organisation | Santander Bank |
Sector | Private |
Country | United States |
Start | 03/2017 |
End | 07/2017 |
Description | Apatmer Group |
Organisation | Aptamer Group |
Country | United Kingdom |
Sector | Private |
PI Contribution | From the grant linked this has led to a new partnership in progress with The Aptamer group (York) for support of grant submission. This grant has provided an active collaboration and we are moving forward with discussions on further applications. We are working on development of hybrid materials using materials from the company. Several publications are in draft where we are improving aptamers through this method. A formal NDA/MTA is in place Aptamer group have supported with in-kind support a fellowship bid (EPSRC Dec 2020) |
Collaborator Contribution | AG are providing sequences for specific targets that we are using for basing the research on. Support for EPSRC Fellowship bid. (Dec 2020) |
Impact | Two publications are under review and should be published in April. Several further are in progress including COVID targeting. |
Start Year | 2015 |
Description | DNA chemistry |
Organisation | University of Massachusetts |
Department | RNA therapeutics institute |
Country | United States |
Sector | Academic/University |
PI Contribution | I have been leading this project (EP/K015095/1) but required a DNA chemist to help develop potential base chemistries. Using the synthesisied sequences prepared by Dr Watts' team I have generated and tested polymeric materials. |
Collaborator Contribution | With Dr Jon Watts I have built a collaboration supporting EP/K015095/1. Dr Watts have provided synthesis and base design work for the progress of this project. Support for EPSRC proposal follow up EP/P026559/1 (at panel 7th March) |
Impact | I have given a seminar at Southampton, and likewise Dr Watts has spoken here at the OU. There are 3 papers in publication, 1 published, 1 accepted and 1 under review on date of completion of this form. The joint work has been presented at a number of conferences. JW has moved from Southampton to UMass. Has supported further work by sample prep. Santander grant awarded for travel for further research |
Start Year | 2013 |
Description | Nanoparticles |
Organisation | University of Leicester |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I have strong links with the research group of Professor Piletsky, recently of Cranfield, but now Leicester Chemistry. We have regular research meetings to discuss current projects and future ideas. We also share equipment and methods. |
Collaborator Contribution | Discussions on nanoparticle production and use of specialized equipment based at Leicester. Support on EPSRC submission (letter of support as project partner) |
Impact | Several papers as found in Publications |
Description | Supermonomer design - David Fulton |
Organisation | Newcastle University |
Department | Institute of Cellular Medicine |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Through the work started with this grant I have generated a working relationship with Dr David Fulton towards developing supermonomers for imprinting using dynamic combinatorial chemistry. This fledgling collaboration towards a Leverhulme bid (submission 1st Apr 2017) which was not successful. Based on this we have worked again, supported by the results of this grant, a further application to EPSRC responsive mode. Submitted October 2020 |
Collaborator Contribution | Joint writing of proposals |
Impact | Grant submission (1st Apr 2017) GRant submission (2nd Oct 2020) |
Start Year | 2016 |
Description | EPSRC (Inspire) meeting |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | Yes |
Geographic Reach | National |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | Engaged with peers and field leaders in discussions on joint collaborative projects, and career trajectory. Inspire bid submitted joint with Kent (Arnold), Durham (Beaumont), Liverpool (Cowan) and York (McKenna). Two further delegates were invited for talks and further collaborative discussions at the OU, Moram (Imperial) and Karenowska (Oxford). The latter of which is still continuing. I have also enaged in a collaborative study on electropolymers with Alexander Cowan (Liverpool) |
Year(s) Of Engagement Activity | 2014 |
Description | EPSRC - building tomorrows leaders |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Invited EPSRC workshop |
Year(s) Of Engagement Activity | 2015 |
Description | EPSRC prioristation panel member |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | EPSCRC chemistry panel member December 2015 |
Year(s) Of Engagement Activity | 2015 |
Description | Invited Talk (Verona) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Seminar at University of Verona |
Year(s) Of Engagement Activity | 2017 |
Description | Lecture Tour (New Zealand) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Funds acquired from NERC CENTA travel scheme to visit New Zealand to give a series of lectures.Lectures at: Auckland University, Waikato University, SCION and Blenheim High School. |
Year(s) Of Engagement Activity | 2017 |
Description | Lecture Tour (USA) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Working from the Santander grant i visited University of Massachusetts and gave a series of talks in both research and education. |
Year(s) Of Engagement Activity | 2017 |
Description | SCI conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | Talk and Poster given by Dr Poma (PDRA) Awarded 1st prize in the poster section. |
Year(s) Of Engagement Activity | 2013 |
URL | http://www.soci.org/Chemistry-and-Industry/Academic-Posters/2013/SCI-Members-Forum-2013/Generation-o... |
Description | Smart Materials |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Industry/Business |
Results and Impact | Through this work i have created a new cross departmental research group which has presented our research at the MRE2018. |
Year(s) Of Engagement Activity | 2018 |
URL | http://www.mre2018.co.uk/ |
Description | Talk (Birmingham) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Postgraduate students |
Results and Impact | Academic talk (Birmingham university) |
Year(s) Of Engagement Activity | 2015 |
Description | Talk (Durham) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Academic invited talk |
Year(s) Of Engagement Activity | 2016 |
Description | Talk (Kent) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | Presented work based on current grant - led to discussions and interest in MIP technique invitation to join a potential collaboration for EPSRC bid (in preparation) |
Year(s) Of Engagement Activity | 2014 |
Description | Talk (Southampton) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | Talk to collaborator and other academics Given that this was my first university a number of academics who taught me were present which has led to interest in my work. Supported current collaboration with Dr Watts and identified potential further collaboration options. |
Year(s) Of Engagement Activity | 2014 |
Description | Talk (Sydney, Australia) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | Research talk to demonstrate the scope of imprinting technologies In talks for potential collaborations and student enquiry interest in visiting my lab |
Year(s) Of Engagement Activity | 2014 |
Description | Talk (University of Newcastle, Australia) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | A lot of interest in the new imprinting methods I am using, from the main groups there. opportunity to return on sabbatical offered |
Year(s) Of Engagement Activity | 2014 |